P681: MATCHING-ADJUSTED INDIRECT COMPARISON OF ASCIMINIB VERSUS OTHER TYROSINE KINASE INHIBITORS IN THIRD-OR-LATER LINE CHRONIC-PHASE CHRONIC MYELOID LEUKEMIA
Authors: Ehab Atallah, Aurore Yocolly, Kejal Jadhav, Teresa Kangappaden, Andrea Damon, Imtiaz A. Samjoo, Devarshi Bhattacharyya
Journal: HemaSphere (2023)

Background: The current standard of care for chronic-phase chronic myeloid leukemia (CP-CML) is tyrosine kinase inhibitors (TKIs). Asciminib, the first specific ABL myristoyl pocket inhibitor, showed promising efficacy and safety results when evaluated against bosutinib in the phase 3 ASCEMBL (NCT03106779) trial at 24 and 48 weeks of follow-up. A recently updated analysis showed that asciminib continued to demonstrate superior efficacy and safety vs bosutinib after 96 weeks of follow-up (Hochhaus 2023). With no head-to-head trials comparing asciminib to other TKIs beyond bosutinib, alternative comparison methods are needed to further clarify treatment recommendations for patients with CP-CML failing ≥2 lines of therapy. Aims: Matching-adjusted indirect comparisons (MAICs) were conducted to compare the efficacy of asciminib with competing TKIs in CP-CML after failure of ≥2 TKIs, using 96-week follow-up data from ASCEMBL. Methods: Unanchored MAICs were conducted to adjust individual patient-level data for asciminib (ASCEMBL; follow-up: ≥96 weeks) to published aggregate data for comparator TKIs (ponatinib [PACE: third- or later line [3L+] cohort], nilotinib [Giles 2010; Ibrahim 2010], and dasatinib [Tan 2019; Rossi 2013; Ibrahim 2010]). The MAICs aimed to adjust for the following variables: number of prior TKIs, resistance/intolerance to prior TKIs, cytogenetic response status, number of mutations, Eastern Cooperative Oncology Group (ECOG) performance score, age, gender and race. Effective sample size (ESS) was calculated to show the degree of overlap between the adjusted asciminib population and the comparator population. Where feasible, major molecular response (MMR), complete cytogenic response (CCyR), and times to MMR and CCyR between asciminib and comparator TKIs were assessed. Additional sensitivity analyses were conducted (e.g., removing ponatinib pretreated patients from ASCEMBL). Results: Asciminib was associated with statistically significant improvements in MMR by 6 (relative risk [RR]: 1.55; 95% confidence interval [CI]: 1.02, 2.36) and 12 months (RR: 1.48; 95% CI: 1.03, 2.14) vs ponatinib. There was no statistically significant difference for CCyR, by 6 months (RR: 1.11; 95% CI: 0.81, 1.52) or 12 months (RR: 0.97; 95% CI: 0.73, 1.28) vs ponatinib. The additional analysis removing ponatinib pretreated patients showed that asciminib had significant improvements in MMR by 6 (RR: 1.68; 95% CI: 1.10, 2.55]) and 12 months (RR: 1.72; 95% CI: 1.20, 2.45) and numerical improvements in CCyR by 6 (RR: 1.15; 95% CI: 0.84, 1.59) and 12 months (RR: 1.03; 95% CI: 0.78, 1.36) vs ponatinib. Removal of patients pre-treated with ponatinib showed that post-adjustment asciminib had favorable results for times to MMR and CCyR by both 6 and 12 months vs ponatinib (Figure). There were no statistically significant differences for asciminib in MMR by 6 months vs dasatinib (RR 1.52; 95% CI: 0.66, 3.53). Asciminib was associated with statistically significant improvements in CCyR by 6 (RR: 3.57; 95% CI: 1.42, 8.98) and 12 months (RR: 2.03; 95% CI: 1.12, 3.67) vs pooled nilotinib/dasatinib. Summary/Conclusion: In the results of the MAICs, asciminib continued to demonstrate mostly favorable outcomes in MMR and CCyR compared with other TKIs for CP-CML. Superior outcomes were especially noted among ponatinib-naïve patients receiving asciminib vs ponatinib. Limitations of the analysis included inability to adjust for all characteristics and limited studies to inform comparisons. Despite these caveats, these results can aid in defining a treatment pathway for patients in CP-CML after failure of ≥2 prior TKIs.Keywords: Molecular response, Tyrosine kinase inhibitor, Chronic myeloid leukemia, Clinical outcome